Gaag et al. Int J Pediatr Res 2015, 1:2 International Journal of ISSN: 2469-5769 Pediatric Research Research Article: Open Access Folic Acid and Iron Supplementation in Children with Insufficient Diets in a Developed Country, a Randomised Controlled Trial E J van der Gaag1*, N Bolk-van Droffelaar2, J van der Palen3 and R Baarsma4 1Paediatrician, Streekziekenhuis Midden Twente, Hengelo, The Netherlands 2General physician, General physician practice, Geesteren, The Netherlands 3Epidemiologist, Medisch Spectrum Twente, The Netherlands 4Paediatrician, Hospital of Polokwane (Pietersburg), Limpopo, South Africa *Corresponding author: E J van der Gaag (Paediatrician), Streekziekenhuis Midden Twente, Postbus 546, 7550 AM Hengelo (Overijssel), The Netherlands, Tel: 0031-887083120, Fax: 0031-887083465, E-mail: [email protected] up to 50% is known with an anaemia caused by iron deficiency [1]. In Abstract the United States the prevalence of anaemia in childhood is decreasing Background: In developed countries, dietary intake of pre- from 7.9% in 1981 to 3.6% in 1994 [2]. During childhood, dietary iron schoolers is sometimes inadequate. Not because of insufficient is the main source for iron stores. Deficiencies are frequently caused provisions, but due to picky eating and behavioural feeding by inadequate qualitative and/or quantitative dietary intake [3,4]. problems. Micronutrient deficiency could be a result, but is most of the time difficult to detect due to failing laboratory evaluations. In developed countries, these deficiencies can also occur in the Iron deficiency is the most common detected nutritional deficiency general population, not due to low-income, but to inadequate intake in children; other deficiencies may be present but are also hidden in childhood. Dietary habits of most children aged 1 to 4 consist because they cannot always be found in routine evaluations. of high consumption of milk and other products low on iron [3]. We therefore studied the supplementation of a single or two Combined with their high growth velocity [5] and picky eating as a micronutrients in clinical and laboratory outcomes. normal stage in childhood it results in a larger risk for micronutrient Methods: A double blind randomised controlled trial was performed deficiencies like iron and folate [4]. At the age of 2, about 50% of the in children aged 1-5 years with a suspicion of micronutrient children are to some extent picky eaters [6]. Studies have shown only deficiencies; expressed in picky eating and clinical complaints like few picky eaters develop a micronutrient deficiency [6]. Micronutrient recurrent infections or tiredness. They were supplemented with deficiencies are difficult to detect due to little early symptoms. Of all either iron alone or iron in combination with folic acid. micronutrient deficiencies, iron deficiency is detected most frequently Results: 83% of the children showed inadequate dietary iron intake by laboratory abnormalities like decreased hemoglobin levels, ferritin and 48% inadequate folic acid with the 3 day food recall evaluation. and Mean Corpuscular Volume (MCV). Clinical parameters like tiredness, the number of infections or antibiotic use improved in almost all children after supplementation As a symptom of this time period, several children suffer from in both groups. Combined iron and folic acid supplementation did a specific disorders like tiredness or recurrent infections without a not have an additive effect compared to iron supplementation alone. known cause. When they are evaluated physically and by laboratory Laboratory parameters like hemoglobin levels, Mean Corpuscular examination, causes like immunologic or hematologic disorders can Volume, Red cell Distribution Width and ferritin levels improved in be ruled out. Usually, from a large group the causes of the clinical all children. problems remain unclear. Conclusions: Despite inadequate dietary intake, folic acid supplementation has no additive effect on iron supplementation We hypothesize that the clinical picture of recurrent infections alone in a developed country. in childhood can be caused by insufficient dietary iron intake, even though laboratory research is not always conclusive. Keywords We investigated an iron deficiency as a possible cause for a group Folic acid deficiency [MeSH], Iron deficiency, Infection [MeSH], of children with recurrent infections without another known cause. Hemoglobin(s) [MeSH], Respiratory infections Methods Introduction Patients Iron deficiency leads to microcytic red blood cells and is the most Children between the age of 1 and 5 years with picky eating common nutritional deficiency in children. In developing countries and clinical complaints like recurrent viral respiratory infections Citation: Gaag EJ, Droffelaar NB, Palen JV, Baarsma R (2015) Folic Acid and Iron Supplementation in Children with Insufficient Diets in a Developed Country, a Randomised Controlled Trial. Int J Pediatr Res 1:009 ClinMed Received: August 17, 2015: Accepted: October 10, 2015: Published: October 13, 2015 International Library Copyright: © 2015 Gaag EJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. and/or subjective complaints of tiredness were included in a period Results of 2 years. Picky eating was defined as children who consume an inadequate variety of foods through rejection of a substantial Group descriptives amount of foods that are familiar (as well as unfamiliar) to them. A total of 50 patients were included with picky eating, unexplained Laboratory research for immunological or haematological disorders recurrent respiratory infections and/or tiredness. No immunologic was conducted according to our protocol [7]. When abnormalities disorders were found. Of these 50 patients; 31 were tired compared to at laboratory research (hemoglobin < 6.6 or immunologic disorders children of their age and 43 suffered from recurrent infections (Table like absent immunoglobulin values) were found, the patient was 1). 27 patients were both tired and suffered from infections. excluded. Children who had conditions like congenital anaemia, hemoglobin disorders or any chronic illness causing the iron For the iron-folate trial, 50 children (32 boys, 18 girls) were deficiency were excluded. Also, when they used iron supplementation included, but due to absence at the second visit, too long periods net prescribed by the researchers, they were excluded. During the first between two visits (> 16 weeks) or incorrect use of medication, 9 visit, children were examined for physical abnormalities and length patient were excluded afterwards for the trial. Of the 41 children, 18 and weight were measured. Standard deviation scores from growth (12 boys, 6 girls) received iron alone and 23 (14 boys, 9 girls) received iron in combination with folic acid. charts were calculated for each child using Growth Analyser (version 3.5. Application Ed. Dutch Growth Foundation, PO Box 23068, 3001 No significant differences were found between patient descriptives KB, Rotterdam, The Netherlands). Parents were asked to answer a of both groups. No apparent signs of malnutrition were found on questionnaire about their child’s health, number of infections, are growth parameters in all patients. they tired compared to other children, and interfering parameters like medication and vitamins. During the second visit length, weight Iron status and hematologic values were measured and parents were requested In the group of 41 children, food recall analysis showed insufficient to answer the questionnaire again (with additional questions about iron intake in 83% of the children and insufficient folic acid intake in side effects). 48%. Of these 41 patients, we searched for signs of iron deficiency with laboratory examination. Since patients with haemoglobin < The patients were included at the pediatric outpatient clinic 6.6 mmol/l were excluded, there were no obvious signs for anaemia of a general hospital, Enschede, The Netherlands. The parents of present. In 12 patients there were one or more signs present for the patients filled out the questionnaires at home, and they were iron deficiency expressed in low MCV, ferritin or elevated Red cell collected at the outpatient clinic by the main researcher. The main distribution width (RDW) (Table 1). When iron was substituted, we (blinded) researcher also performed the measurements for growth found a hemoglobin increase of more than 1 g/dL in 18 patients. 6 of and laboratory research. Another researcher had no patient contact these 18 patients were already detected with one or more laboratory and evaluated the blinded data. signs of iron deficiency, the others showed no abnormalities in their Iron status initial laboratory values. Since half of the children received iron and folate supplementation, we only analyzed the patients who received Of all patients, hematologic parameters (hemoglobin levels, iron supplementation for the iron deficiency parameters. When we MCV, hematocrit, reticulocytes and ferritin) were determined. would use the parameters of all children, we could not differentiate Hemoglobin levels below 6.6 mmol/l (10.5 g/dl) were defined anemic. between the effects of iron or folate supplementation. We saw all MCV levels below 70 (children between 1 and 2 years) or below 75 laboratory parameters improved significantly except for the